This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overarching goal of this project is to modify our existing fear inhibition paradigm to permit its use longitudinally, first to investigate (pre- and post-surgery) which specific orbital frontal sectors are involved in the acquisition and expression of conditioned inhibition (safety signal learning) in male and female adult monkeys (R21 phase) and second follow longitudinally when orbital frontal regulation of conditioned inhibition emerged in primates of both sexes. We have ordered two new conditioning boxes to allow the testing of the animals of the present project and have modified these boxes to allow testing using multiple visual cues delivered via a computer screen. We have also programmed the delivery of the conditioned and unconditioned stimuli and have already acquired 9 female and 2 male adult rhesus monkeys to begin the experiments. Excessive fear and anxiety, along with an inability to overcome these emotions, are defining characteristics of many psychiatric disorders such as phobias, panic disorder, and post-traumatic stress disorder. This paradigm will thus allow us, and the field, to look at the anatomy, neurotransmitters, and molecular events that mediate and modulate safety signal learning in rodents that can be used to develop specific hypotheses that can then be tested in rhesus monkeys. Animal models of fear conditioning and fear inhibition provide useful tools for the study of these phenomena. We believe this will establish a new and important translational approach to eventually develop novel treatments for disorders such as post traumatic stress disorder (PTSD), where an inability to respond to safety signals is one of its core symptoms.